Responsive electrical stimulation for movement disorders

ABSTRACT

An implantable neurostimulator system for treating movement disorders includes a sensor, a detection subsystem capable of identifying episodes of a movement disorder by analyzing a signal received from the sensor, and a therapy subsystem capable of supplying therapeutic electrical stimulation to treat the movement disorder. The system treats movement disorders by detecting physiological conditions characteristic of an episode of symptoms of the movement disorder and selectively initiating therapy when such conditions are detected.

CROSS-REFERENCE TO RELATED APPLICATION

This is a divisional of U.S. Ser. No. 14/059,090, filed Oct. 21, 2013,which is a continuation of U.S. Ser. No. 12/881,143, filed Sep. 13,2010, now U.S. Pat. No. 8,594,795, which is a continuation of U.S. Ser.No. 11/517,783, filed Sep. 8, 2006, now U.S. Pat. No. 7,813,802, whichis a continuation of U.S. Ser. No. 10/072,669, filed Feb. 2, 2002, nowU.S. Pat. No. 7,110,820, each of which is hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

The invention relates to systems and methods for applying responsiveelectrical stimulation for treating movement disorders, and moreparticularly to systems and methods employing an implantable responsiveneurostimulator to deliver electrical stimulation therapy in response todetected physiological conditions, either alone or in combination withother therapies.

BACKGROUND OF THE INVENTION

Movement disorders, i.e. neurological diseases or other problems thatresult in movement or muscle control problems are debilitating to agreat number of individuals worldwide. In general, various movementdisorders are characterized by uncontrolled or poorly controlledmovement, involuntary movement, an inability or reduced ability to move,or improper muscle tone.

Parkinson's Disease is generally characterized by tremor, an involuntarymovement of the limbs and extremities that leads to an inability toperform normal daily life activities. It is believed that the symptomsof Parkinson's Disease are caused at least in part by a loss ofdopaminergic neurons in the substantia nigra, a brain structure with aninhibitory effect on movement. Other symptoms of Parkinson's Diseaseinclude rigidity (undesired increased muscle tone, often leading to a“locking” effect in the limbs) and bradykinesia (slower-than-desiredmovements, and difficulty in initiating movements).

Essential Tremor, as its name suggests, is also characterized primarilyby tremor in the limbs and extremities. Tremor can also result as asymptom of Multiple Sclerosis and other diseases and disorders.

Other movement disorders are characterized by different symptoms.Dyskinesias, such as Huntington's Chorea, result in other forms ofunwanted movement. Huntington's Chorea, in particular, is a congenitaldisorder that causes undesired “dance-like” movements of the limbs. Itis believed to be caused by degeneration of the striatum. Hemiballismus,another dyskinesia, causes flailing of the limbs on one side of the bodyand is believed to be caused by degeneration of the subthalamic nucleus.

While drug therapy provides good results for a substantial number ofpatients suffering from various movement disorders, particularly in theearly stages before the disorders have progressed, there are somedisadvantages to using drugs. In particular, patient compliance isparticularly difficult to achieve when complex drug regimens arenecessary to maintain an effective serum concentration. If drug levelsare too low, the therapy may be ineffective; high levels can bedamaging—they may cause serious side effects or even exacerbate thepatient's movement disorders.

Surgery has also shown some promise and is effective with some patients,especially since there are fewer ongoing patient compliance issues(although patients who have had resective brain surgery are frequentlykept on drug therapy as well). For example, lesions can be produced inthe thalamus, globus pallidus, and other brain structures in an attemptto regulate patients' symptoms. However, clearly, resective brainsurgery is irreversible and risky—neurological deficits have been knownto occur.

Accordingly, described herein are two types of disorders of the humanbrain that have been shown to be effectively treated by the use ofelectrical stimulation. A first type of disorder is involuntary motiondisorders such as the tremor associated with Parkinson's disease,familial tremor, tics or any other disorder that results in a shaking ofa patient's hand, head or any other body part. A second type of disorderis associated with loss of muscular control as for example dystonia,spasticity or rigidity.

Continuous deep brain stimulation, particularly in the ventralisintermedius (Vim) nucleus of the thalamus, also has been shown toprovide some relief from the symptoms of various movement disorders.However, this approach has resulted in some unpleasant side effects, inparticular paresthesias, numbness, and slurring of speech. Moreover, arelatively small implantable device capable of performing continuousstimulation would tend to have a shorter battery life than would bedesirable. Unlike other surgical treatments, continuous deep brainstimulation is reversible, in the event the side effects or neurologicaldeficits resulting therefrom are more debilitating or unpleasant thanthe movement disorder. See, e.g., A. L. Benabid et al., “Long-TermElectrical Inhibition of Deep Brain Targets in Movement Disorders,”Movement Disorders 1998, 13 (Supp. 3): 119-25; and R. E. Gross et al.,“Advances in Neurostimulation for Movement Disorders,” NeurologicalResearch 2000, 22: 247-258.

Deep brain recordings from patients with tremor have shown an abnormalrhythmic electrical activity in the thalamus, globus pallidus, andsubthalamic nucleus at a frequency of approximately 3-5 Hz. Thisrhythmic activity is associated with tremor, i.e., there is asubstantially constant frequency and phase relationship between tremorand the electrophysiological activity. When electrical stimulation isapplied in this same region of the brain where the 3-5 Hz signal isdetected, the involuntary motion can be eliminated or at leastmoderated. Applying an electrical signal at 30-180 Hz using 300microsecond biphasic pulses has been shown to eliminate or attenuatetremor. Stimulation by deep brain electrodes at 60-70 Hz using 300microsecond biphasic pulses at 3-6 volts has been shown to cause areduction in spasticity thereby allowing more normal movements.

Even voluntary and intentional movement causes observable signals in thethalamus; tremor is manifested by regular oscillations at apatient-specific frequency. It is of course understood that otherregimens of electrical stimulation can also be used for treatinginvoluntary motion and muscle tone disorders.

Both the detection of abnormal deep brain electrical signals and thecontrol of abnormal motion and motor control disorders have beenreported by Cooper, Upton and Amin. See I. S. Cooper et al., “ChronicCerebellar Stimulation (CCS) and Deep Brain Stimulation (DBS) ininvoluntary movement disorders,” Applied Neurophysiology 1982, 45(3):209-17. There is no currently available device that can provide eitheror both responsive and/or continuous electrical stimulation via deepbrain electrodes to reduce or eliminate involuntary motion disordersand/or muscle tone disorders. The Medtronic Activa implantable pulsegenerator is now in use for Parkinson's disease. The Activa providesperiodic or continuous stimulation to the thalamus through deep brainelectrodes but has no responsive capabilities. In U.S. Pat. No.6,016,449, Fischell et al. describe a sophisticated cranially implantedneurostimulator with responsive electrical stimulation capabilities,generally described as being used in the treatment of epilepsy.

SUMMARY OF THE INVENTION

The invention is a responsive system, at least part of which is animplantable neurostimulator, suited to be implanted within a humanpatient, for decreasing involuntary motion tremor and other symptomsassociated with Parkinson's disease and other diseases of the brain thattend to cause abnormal movements or inappropriate muscle tone. Theimplanted neurostimulator of the present invention can also generateeither or both continuous and/or responsive stimulation to treat muscletone disorders that include (but are not limited to) dystonia,spasticity, and rigidity.

The implanted portion of the system generally includes an electrodearray that is placed deep within the patient's brain. For oneembodiment, a control module is placed into a section of the craniumwhere cranial bone has been removed. The control module is electricallyconnected to deep brain electrodes by means of leads that run beneaththe patient's scalp or within the patient's cranium. A typical locationfor the electrodes would be in the vicinity of the thalamus, theinternal capsule, or the basal ganglia (particularly the Globus PallidusInternus and the Subthalamic Nucleus).

As explained above, it has been shown that prior to a visible tremorbeing experienced by (for example) a Parkinson's disease patient, thereis likely to be a detectable electrical signal correlated with thetremor that is detectable in the vicinity of the thalamus. This signalgenerally starts at a low amplitude that does not cause an observableclinical tremor. Over a period of a few seconds, the amplitude continuesto increase. When the amplitude reaches a certain level, the patientwill begin to show an observable tremor. As soon a therapy criterion isobserved (e.g., when the oscillation amplitude exceeds a thresholdlevel), a neurostimulator according to the invention causes a responsiveelectrical signal to be applied to terminate the undesired tremoroscillations. When such an electrical signal is applied, previousstudies have shown that involuntary motion can be eliminated or at leastreduced in severity, even after stimulation is removed. See, e.g., S.Blond et al., “Control of Tremor and Involuntary Movement Disorders byChronic Stereotactic Stimulation of the Ventral Intermediate ThalamicNucleus,” Journal of Neurosurgery 1992, 77: 62-68.

The implantable neurostimulator of the invention is capable of storingand transmitting data, thereby allowing the refinement of devicesettings. Accordingly, data received from an implanted neurostimulatorwill, over time, help each individual patient. Moreover, theaccumulation of data from many treated patients over time willfacilitate development of optimal programs for detection and stimulationto treat numerous movement and muscle tone disorders.

In spasticity, one problem is the unwanted contraction of muscles thatshould relax during movement. Detection of movement of the limb (viaEEG, EMG, or accelerometer, for example) and responsive stimulation ofthe thalamus or internal capsule can be used to reduce contraction ofmuscles that oppose the desired movement. It is envisioned that thespasticity of one side of the body opposite to brain damage can bereduced by thalamic and internal capsule stimulation. A reduction inspasticity or rigidity will frequently make it possible for a patient tomove, but with more voluntary effort than in a person without spasticityor rigidity. Accordingly, stimulation and therapy according to theinvention will tend to help those who have some ability to move underthe spasticity.

It should be understood that the implanted portion of the system couldinclude bilateral electrical signal detection electrodes and bilateralelectrodes for providing responsive stimulation. It should also beunderstood that the electronic circuitry of the implanted portion of thesystem (called a “control module”) can be programmed by externalequipment to adjust many of the control module's functions, includingboth detection and therapy delivery. For example, the threshold voltagelevel of the signal detected by the brain electrodes can be adjusted toturn on responsive stimulation only after a pre-programmed amplitudelevel has been exceeded. Also the parameters of the responsivestimulation signal applied by the deep brain electrodes can beprogrammed by via external equipment into the electronic circuitry ofthe control module. For example, the frequency, amplitude and pulsetrain characteristics of the control module output circuitry isprogrammable by the means of electrical equipment that is external tothe patient. Furthermore, the system can be used to select whichelectrodes of the array of electrodes are used for signal detection andwhich are to be used for responsive stimulation. It should be understoodthat the same electrodes can be used both for signal detection and forresponsive or programmed stimulation.

It is envisioned that the control module will also include thecapability for multi-channel recording of the electrical input signalsthat it receives from any of the system's deep brain electrodes, whichsignal is a form of the patient's electroencephalogram (EEG).Additionally, electromyographic (EMG) voltage signals from muscles thatare being controlled by that portion of the brain that is beingstimulated, as well as other types of signals (such as from anaccelerometer) may also be recorded within the memory of the controlmodule. The control module can be programmed to determine whichelectrode(s) will be the source of the EEG signal to be recorded. Theexternal equipment can cause the control module to read out either orboth real time and/or recorded EEG or EMG signals. Other telemetry datathat can be read out includes, but is not limited to, battery voltage,the time when a data recording was made, the setting of the thresholddetection voltage and a tabulation of which of the multiple electrodesof the implanted portion of the system are being used for signaldetection and which electrodes are being used for stimulation of thebrain tissue.

It should be understood that, as compared to continuous stimulation,responsive stimulation has several distinct advantages. A firstadvantage is decreased use of electrical energy thereby prolongingbattery life. A second advantage is reduced habituation, the build-up oftolerance of the brain tissue exposed to the electrical stimulationsignal. Reduced tolerance build-up is expected because the stimulationsignal is not continuously applied but is applied only when conditionsdictate. Finally, and of primary importance in many patients, to theextent continuous stimulation may result in undesired side effects, suchas uncomfortable sensory effects and slurring of speech, selectivelyintermittent programmed and responsive stimulation can reduce those sideeffects.

An embodiment of the present invention also includes an externallylocated patient operated initiating device that can be used by thepatient to operate the implanted control module. Specifically, thepatient operated initiating device can be used to turn on or off thestimulation and/or other functions of the control module if thatfunction is or is not desired. For example, the patient operatedinitiating device can be used to turn off responsive or continuousstimulation if the patient is about to go to sleep or is merely watchingtelevision or doing any other activity where an involuntary motion ormuscle tone disorder is not disturbing to the patient. This function hasthe potential to increase battery longevity even further. The patientoperated initiating device could also be used for other functions suchas retaining in memory a particular EEG signal portion that the patientbelieves to be of interest in the treatment of his or her disorder.

As motion disorders rarely occur during sleep, it is envisioned that theimplanted device could have an orientation sensor that can determinewhether the patient is lying down, sitting, or standing up. Such adetector could allow for reduced power consumption. It is alsoenvisioned that with electrodes deep into the brain, specific sleep EEGpatterns can be recorded and a “sleep detector” could be programmed intothe detection subsystem within the control module to allow stimulationto be disabled during sleep. REM sleep has specific detectable EEGpatterns that are well known. As stated above, an alternative method ofreducing power consumption during sleep is to have the internal clock orthe patient using a patient control device, turn off the neurostimulatorfor a specified period during sleep.

It is further envisioned that in addition to providing electricalstimulation, an implantable neurostimulator according to the inventioncan include an implanted drug pump to responsively (or programmably)release a medication to assist in the control of an involuntary motionor a muscle tone disorder. Still further, it is envisioned that acombination of electrical stimulation and medication release can be usedfor responsively treating involuntary motion or muscle tone disorders.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects, features, and advantages of the invention willbecome apparent from the detailed description below and the accompanyingdrawings, in which:

FIG. 1 is a functional block diagram illustrating structures of thehuman brain believed responsible for voluntary and involuntary movement;

FIG. 2 is a block diagram of an implantable neurostimulator systemaccording to the invention used in conjunction with external equipment;

FIG. 3 is a schematic illustration of a patient's cranium showing theimplantable neurostimulator of FIG. 2 as implanted, including a leadextending to the patient's brain;

FIG. 4 is a block diagram of the implantable neurostimulator of FIG. 2for responsive treatment of movement disorders according to theinvention;

FIG. 5 is a block diagram illustrating data structures stored in amemory subsystem of an implantable neurostimulator according to theinvention;

FIG. 6 includes two waveforms depicting tremor observed in a patient'sbrain and in the same patient's limb, illustrating frequency and phaserelationships between the two waveforms;

FIG. 7 is a flow chart illustrating a process performed in detecting aneurological event characteristic of a movement disorder in a systemaccording to the invention;

FIG. 8 is a flow chart illustrating a process performed in detectingtremor via thresholded signal amplitude in a system according to theinvention;

FIG. 9 is a flow chart illustrating a process performed in detectingtremor via the identification of signal frequency and phaserelationships in a system according to the invention;

FIG. 10 is a graph of an exemplary intracranial EEG signal, illustratingthe extraction of half waves from the signal for neurological eventdetection purposes;

FIG. 11 is a flow chart illustrating a process performed in detectingtremor via the identification of half waves in an EEG signal in a systemaccording to the invention;

FIG. 12 is a graph of an exemplary intracranial EEG signal, illustratingthe calculation of an area function representative of the signal forneurological event detection purposes;

FIG. 13 is a flow chart illustrating a process performed in detectingtremor via the identification of half waves in a signal representativeof signal activity in a system according to the invention;

FIG. 14 illustrates several possible stimulation waveformsadvantageously employed to control movement disorders with a systemaccording to the invention;

FIG. 15 is a flow chart illustrating a process performed in applyingelectrical stimulation therapy for a movement disorder with a systemaccording to the invention;

FIG. 16 illustrates correlating the application of electricalstimulation therapy with observed tremor oscillations with a systemaccording to the invention;

FIG. 17 is a flow chart illustrating a process performed in correlatingthe application of electrical stimulation therapy to a detectedneurological event; and

FIG. 18 is a flow chart illustrating a process performed in adjustingelectrical stimulation therapy parameters according to a detectedneurological event.

DETAILED DESCRIPTION OF THE INVENTION

The invention is described below, with reference to detailedillustrative embodiments. It will be apparent that a system according tothe invention may be embodied in a wide variety of forms. Consequently,the specific structural and functional details disclosed herein arerepresentative and do not limit the scope of the invention.

FIG. 1 illustrates several portions of the human brain that are believedto be the primary structures involved in voluntary and involuntarymovement. An implantable neurostimulator 110 according to the invention,which will be described in additional detail below, interacts with thesestructures to control movement disorders.

Movements are initiated and executed via the cerebral cortex 112, inparticular the motor cortex. However, movements are controlled andregulated through inhibitory inputs from the basal ganglia 113, acollection of brain structures 114-122 described in general below.

The striatum 114, which includes the caudate and putamen, receivesinputs from the cerebral cortex 112. In turn, the striatum communicateswith the globus pallidus 116, and in particular provides inputs to theglobus pallidus externus (GPe) 118 and the globus pallidus internus(GPi) 120. The GPi 120 then provides its information to the thalamus122, which tends to regulate and inhibit activity in the cerebral cortex112 as necessary for controlled movement. Concurrently, the GPe 118 alsosends information to the subthalamic nucleus 124, which then controlsthe activity of the GPi 120 (and hence the thalamus 122). The striatum114 also communicates with the substantia nigra 126—it sends inputs tothe substantia nigra pars compacta (SNc) 128 and the substantia nigrapars reticulata (SNr) 130, and receives feedback from the SNc 128.

In individuals without movement disorders, this complex scheme ofinhibitory regulation provided by the thalamus 122 to the cerebralcortex 112 permits finely controlled muscle movements. However, inpatients with movement disorders, dysfunction of one or more structuresof the basal ganglia contributes to the symptoms of uncontrolled orpoorly controlled movements. Accordingly, because these structures ofthe basal ganglia generally collectively provide an inhibitory effect tothe cerebral cortex, several of the movement disorders described hereinare generally characterized by tremor, chorea, and other forms ofundesired and involuntary movement.

It has been found (by Cooper et al., referenced above, among others)that electrical stimulation of various basal ganglia structures canresult in relief from certain symptoms of movement disorders. Howevertraditional attempts at electrical stimulation have encountered sideeffects and have the disadvantages noted above. Accordingly, a systemaccording to the invention is enabled to provide responsive treatment,only when necessary, by providing the implantable neurostimulator 110with detection capabilities and stimulation capabilities. As withtraditional non-responsive devices, stimulation may be advantageouslyapplied to the GPi 120, the thalamus 122, the subthalamic nucleus 124,or any other structure of the basal ganglia (or elsewhere in the brain)that provides relief.

It should be noted that the functional relationships among various brainstructures are generally not very well understood, and that theforegoing description is intended for purposes of illustration of theinvention and not as a definitive guide to brain activity involved inmovement.

As stated above, and as illustrated in FIG. 2, a neurostimulatoraccording to the invention operates in conjunction with externalequipment. The implantable neurostimulator 110 is mostly autonomous(particularly when performing its usual sensing, detection, andstimulation capabilities), but preferably includes a selectablepart-time wireless link 210 to external equipment such as a programmer212. In the disclosed embodiment of the invention, the wireless link 210is established by moving a wand (or other apparatus) havingcommunication capabilities and coupled to the programmer 212 intocommunication range of the implantable neurostimulator 110. Theprogrammer 212 can then be used to manually control the operation of thedevice, as well as to transmit information to or receive informationfrom the implantable neurostimulator 110. Several specific capabilitiesand operations performed by the programmer 212 in conjunction with thedevice will be described in further detail below.

The programmer 212 is capable of performing a number of advantageousoperations in connection with the invention. In particular, theprogrammer 212 is able to specify and set variable parameters in theimplantable neurostimulator 110 to adapt the function of the device tomeet the patient's needs, upload or receive data (including but notlimited to stored EEG waveforms, parameters, or logs of actions taken)from the implantable neurostimulator 110 to the programmer 212, downloador transmit program code and other information from the programmer 212to the implantable neurostimulator 110, or command the implantableneurostimulator 110 to perform specific actions or change modes asdesired by a physician operating the programmer 212. To facilitate thesefunctions, the programmer 212 is adapted to receive clinician input 214and provide clinician output 216; data is transmitted between theprogrammer 212 and the implantable neurostimulator 110 over the wirelesslink 210.

The programmer 212 may be used at a location remote from the implantableneurostimulator 110 if the wireless link 210 is enabled to transmit dataover long distances. For example, the wireless link 210 may beestablished by a short-distance first link between the implantableneurostimulator 110 and a transceiver, with the transceiver enabled torelay communications over long distances to a remote programmer 212,either wirelessly (for example, over a wireless computer network) or viaa wired communications link (such as a telephonic circuit or a computernetwork).

The programmer 212 may also be coupled via a communication link 218 to anetwork 220 such as the Internet. This allows any information uploadedfrom the implantable neurostimulator 110, as well as any program code orother information to be downloaded to the implantable neurostimulator110, to be stored in a database 222 at one or more data repositorylocations (which may include various servers and network-connectedprogrammers like the programmer 212). This would allow a patient (andthe patient's physician) to have access to important data, includingpast treatment information and software updates, essentially anywhere inthe world that there is a programmer (like the programmer 212) and anetwork connection. Alternatively, the programmer 212 may be connectedto the database 222 over a trans-telephonic link.

In yet another alternative embodiment of the invention, the wirelesslink 210 from the implantable neurostimulator 110 may enable a transferof data from the neurostimulator 110 to the database 222 without anyinvolvement by the programmer 212. In this embodiment, as with others,the wireless link 210 may be established by a short-distance first linkbetween the implantable neurostimulator 110 and a transceiver, with thetransceiver enabled to relay communications over long distances to thedatabase 222, either wirelessly (for example, over a wireless computernetwork) or via a wired communications link (such astrans-telephonically over a telephonic circuit, or over a computernetwork).

In the disclosed embodiment, the implantable neurostimulator 110 is alsoadapted to receive communications from an initiating device 224,typically controlled by the patient or a caregiver. Accordingly, patientinput 226 from the initiating device 224 is transmitted over a wirelesslink to the implantable neurostimulator 110; such patient input 226 maybe used to cause the implantable neurostimulator 110 to switch modes (onto off and vice versa, for example) or perform an action (e.g., store arecord of EEG data). Preferably, the initiating device 224 is able tocommunicate with the implantable neurostimulator 110 through thecommunication subsystem 434 (FIG. 4), and possibly in the same mannerthe programmer 212 does. The link may be unidirectional (as with themagnet and GMR sensor described above), allowing commands to be passedin a single direction from the initiating device 224 to the implantableneurostimulator 110, but in an alternative embodiment of the inventionis bi-directional, allowing status and data to be passed back to theinitiating device 224. Accordingly, the initiating device 224 may be aprogrammable PDA or other hand-held computing device, such as thedevices manufactured by Palm, Inc. under the marks “PALM PILOT” and“POCKETPC.” However, a simple form of initiating device 224 may take theform of a permanent magnet, if the communication subsystem 434 isadapted to identify magnetic fields and interruptions therein ascommunication signals.

The implantable neurostimulator 110 generally interacts with theprogrammer 212 as described below. Data stored in the memory subsystem431 can be retrieved by the patient's physician through the wirelesslink 210, which operates through the communication subsystem 434 of theimplantable neurostimulator 110. In connection with the invention, asoftware operating program run by the programmer 212 allows thephysician to read out a history of events detected including EEGinformation before, during, and after each event, as well as specificinformation relating to the detection of each event (such as, in oneembodiment, the time-evolving energy spectrum of the patient's EEG). Theprogrammer 212 also allows the physician to specify or alter anyprogrammable parameters of the implantable neurostimulator 110. Thesoftware operating program also includes tools for the analysis andprocessing of recorded EEG records to assist the physician in developingoptimized tremor detection parameters for each specific patient.

In an embodiment of the invention, the programmer 212 is primarily acommercially available PC, laptop computer, or workstation having a CPU,keyboard, mouse and display, and running a standard operating systemsuch as WINDOWS by Microsoft Corporation, Linux, UNIX by The OpenCompany Limited Corporation, or MAC OS by Apple Computer, Inc. It isalso envisioned that a dedicated programmer apparatus with a customsoftware package (which may not use a standard operating system) couldbe developed.

When running the computer workstation software operating program, theprogrammer 212 can process, store, play back and display on the displaythe patient's EEG signals, as previously stored by the implantableneurostimulator 110 of the implantable neurostimulator device.

The computer workstation software operating program also has thecapability to simulate the detection and prediction of sensor signalactivity representative of movement disorders, such as the tremordescribed herein. Included in that capability, the software operatingprogram of the present invention has the capability to allow a clinicianto create or modify a patient-specific collection of informationcomprising, in one embodiment, algorithms and algorithm parameters forthe detection of relevant sensor signal activity. The patient-specificcollection of detection algorithms and parameters used for neurologicalactivity detection according to the invention will be referred to hereinas a detection template or patient-specific template. Thepatient-specific template, in conjunction with other information andparameters generally transferred from the programmer to the implanteddevice (such as stimulation parameters, time schedules, and otherpatient-specific information), make up a set of operational parametersfor the neurostimulator.

Following the development of a patient specific template on theworkstation 212, the patient-specific template would be downloadedthrough the wireless link 210 from the programmer 212 to the implantableneurostimulator 110.

The patient-specific template is used by the detection subsystem 423 andthe CPU 432 of the implantable neurostimulator 110 to detect activityrepresentative of a symptom of a movement disorder in the patient's EEGsignals (or other sensor signals), which can be programmed by aclinician to result in responsive stimulation of the patient's brain, aswell as the storage of EEG records before and after the detection,facilitating later clinician review.

Preferably, the database 222 is adapted to communicate over the network220 with multiple programmers, including the programmer 212 andadditional programmers 228, 230, and 232. It is contemplated thatprogrammers will be located at various medical facilities andphysicians' offices at widely distributed locations. Accordingly, ifmore than one programmer has been used to upload EEG records from apatient's implantable neurostimulator 110, the EEG records will beaggregated via the database 222 and available thereafter to any of theprogrammers connected to the network 220, including the programmer 212.

The implantable neurostimulator device 110, as implanted intracranially,is illustrated in greater detail in FIG. 3. The device 110 is affixed inthe patient's cranium 314 by way of a ferrule 316. The ferrule 316 is astructural member adapted to fit into a cranial opening, attach to thecranium 314, and retain the device 110.

To implant the device 110, a craniotomy is performed in the parietalbone anterior to the lambdoidal suture 312 to define an opening 318slightly larger than the device 110. The ferrule 316 is inserted intothe opening 318 and affixed to the cranium 314, ensuring a tight andsecure fit. The device 110 is then inserted into and affixed to theferrule 316.

As shown in FIG. 3, the device 110 includes a lead connector 320 adaptedto receive one or more electrical leads, such as a first lead 322. Thelead connector 320 acts to physically secure the lead 322 to the device110, and facilitates electrical connection between a conductor in thelead 322 coupling an electrode to circuitry within the device 110. Thelead connector 320 accomplishes this in a substantially fluid-tightenvironment with biocompatible materials.

The lead 322, as illustrated, like other leads for use in a system ormethod according to the invention, is a flexible elongated member havingone or more conductors. As shown, the lead 322 is coupled to the device110 via the lead connector 320, and is generally situated on the outersurface of the cranium 314 (and under the patient's scalp), extendingbetween the device 110 and a burr hole 324 or other cranial opening,where the lead 322 enters the cranium 314 and is coupled to a depthelectrode implanted in a desired location in the patient's brain (suchas the GPi 120, the thalamus 122, or the subthalamic nucleus 124). Ifthe length of the lead 322 is substantially greater than the distancebetween the device 110 and the burr hole 324, any excess may be urgedinto a coil configuration under the scalp. As described in U.S. Pat. No.6,006,124 to Fischell, et al. for Means and Methods for the Placement ofBrain Electrodes, which is hereby incorporated by reference as thoughset forth in full herein, the burr hole 324 is sealed after implantationto prevent further movement of the lead 322; in an embodiment of theinvention, a burr hole cover apparatus is affixed to the cranium 314 atleast partially within the burr hole 324 to provide this functionality.

The device 110 includes a durable outer housing 326 fabricated from abiocompatible material. Titanium, which is light, extremely strong, andbiocompatible, is used in analogous devices, such as cardiac pacemakers,and would serve advantageously in this context. As the device 110 isself-contained, the housing 326 encloses a battery and any electroniccircuitry necessary or desirable to provide the functionality describedherein, as well as any other features. As will be described in furtherdetail below, a telemetry coil may be provided outside of the housing326 (and potentially integrated with the lead connector 320) tofacilitate communication between the device 110 and the external devicesdescribed above with reference to FIG. 2.

The neurostimulator configuration described herein and illustrated inFIG. 3 provides several advantages over alternative designs. First, theself-contained nature of the neurostimulator substantially decreases theneed for access to the device 110, allowing the patient to participatein normal life activities. Its small size and intracranial placementcauses a minimum of cosmetic disfigurement. The device 110 will fit inan opening in the patient's cranium, under the patient's scalp, withlittle noticeable protrusion or bulge. The ferrule 316 used forimplantation allows the craniotomy to be performed and fit verifiedwithout the possibility of breaking the device 110, and also providesprotection against the device 110 being pushed into the brain underexternal pressure or impact. A further advantage is that the ferrule 316receives any cranial bone growth, so at explant, the device 110 can bereplaced without removing any bone screws—only the fasteners retainingthe device 110 in the ferrule 316 need be manipulated.

An overall block diagram of the device 110 used for measurement,detection, and treatment according to the invention is illustrated inFIG. 4. Inside the housing 326 (FIG. 3) of the device 110 are severalsubsystems making up a control module 410. The control module 410 iscapable of being coupled to a plurality of electrodes 412, 414, 416, and418 (each of which may be connected to the control module 410 via a leadfor sensing, stimulation, or both. In the illustrated embodiment, thecoupling is accomplished through the lead connector 320 (FIG. 3).Although four electrodes are shown in FIG. 4, it should be recognizedthat any number is possible, and in the embodiment described in detailbelow, eight electrodes are used. In fact, it is possible to employ anembodiment of the invention that uses a single lead with at least twoelectrodes, or two leads each with a single electrode (or with a secondelectrode provided by a conductive exterior portion of the housing 326in one embodiment), although bipolar sensing between two closely spacedelectrodes on a lead is preferred to minimize common mode signalsincluding noise.

The electrodes 412-418 are connected to an electrode interface 420.Preferably, the electrode interface is capable of selecting eachelectrode as required for sensing and stimulation. The electrodeinterface 420 also may provide any other features, capabilities, oraspects, including but not limited to amplification, isolation, andcharge-balancing functions, that are required for a proper interfacewith neurological tissue and not provided by any other subsystem of thedevice 110. The electrode interface 420, an external sensor 421, and aninternal sensor 422 are all coupled to a detection subsystem 423; theelectrode interface 420 is also connected to a therapy subsystem 424.

The detection subsystem 423 includes an EEG analyzer function. The EEGanalyzer function is adapted to receive EEG signals from the electrodes412-418, through the electrode interface 420, and to process those EEGsignals to identify neurological activity indicative of tremor,involuntary movement, or any other symptom of a movement disorder;various inventive methods for performing such detection are described indetail below.

The detection subsystem may optionally also contain further sensing anddetection capabilities, including but not limited to parameters derivedfrom other physiological conditions (such as electrophysiologicalparameters, temperature, blood pressure, etc.), which may be sensed bythe external sensor 421 or the internal sensor 422. These conditionswill be discussed in additional detail below. In particular, it may beadvantageous to provide an accelerometer or an EMG sensing electrode asthe external sensor at a location remote from the implantableneurostimulator 110 (e.g., in one of the patient's limbs that is subjectto tremor). The external sensor 421 can be connected to theneurostimulator 110 (and the detection subsystem 423) by a lead or bywireless communication, such as a wireless intrabody signalingtechnique. To detect head tremor or orientation (e.g., for sleepdetection), an accelerometer might be used as the internal sensor 422.Other sensors, such as for temperature, blood pressure, or drugconcentration might be implemented as part of the external sensor 421 orthe internal sensor 422. Other sensor configurations are of coursepossible and are deemed within the scope of the invention.

The therapy subsystem 424 is primarily capable of applying electricalstimulation to neurological tissue through the electrodes 412-418. Thiscan be accomplished in any of a number of different manners. Forexample, it may be advantageous in some circumstances to providestimulation in the form of a substantially continuous stream of pulses,or on a scheduled basis. This form of stimulation, referred to herein asprogrammed stimulation, is provided by a programmed stimulation function426 of the therapy subsystem 424. Preferably, therapeutic stimulation isalso provided in response to abnormal events detected by the dataanalysis functions of the detection subsystem 422. This form ofstimulation, namely responsive stimulation, is provided by a responsivestimulation function 428 of the therapy subsystem 424.

As illustrated in FIG. 4, the therapy subsystem 424 and the dataanalysis functions of the detection subsystem 423 are in communication;this facilitates the ability of therapy subsystem 424 to provideresponsive stimulation as well as an ability of the detection subsystem42 to blank the amplifiers while stimulation is being performed tominimize stimulation artifacts. It is contemplated that the parametersof the stimulation signal (e.g., frequency, duration, waveform) providedby the therapy subsystem 424 would be specified by other subsystems inthe control module 410, as will be described in further detail below.

In an embodiment of the invention, the therapy subsystem 424 is alsocapable of a drug therapy function 429, in which a drug is dispensedfrom a drug dispenser 430. As with electrical stimulation, thiscapability can be provided either on a programmed basis (orcontinuously) or responsively, after an event of some kind is detectedby the detection subsystem 423.

Also in the control module 410 is a memory subsystem 431 and a centralprocessing unit (CPU) 432, which can take the form of a microcontroller.The memory subsystem is coupled to the detection subsystem 423 (e.g.,for receiving and storing data representative of sensed EEG signals andother sensor data), the therapy subsystem 424 (e.g., for providingstimulation waveform parameters to the stimulation subsystem), and theCPU 432, which can control the operation of the memory subsystem 431. Inaddition to the memory subsystem 431, the CPU 432 is also connected tothe detection subsystem 423 and the therapy subsystem 424 for directcontrol of those subsystems.

Also provided in the control module 410, and coupled to the memorysubsystem 431 and the CPU 432, is a communication subsystem 434. Thecommunication subsystem 434 enables communication between theimplantable neurostimulator device 110 (FIG. 1) and the outside world,particularly the external programmer 212 (FIG. 2). As set forth above,the disclosed embodiment of the communication subsystem 434 includes atelemetry coil (which may be situated outside of the housing 326)enabling transmission and reception of signals, to or from an externalapparatus, via inductive coupling. Alternative embodiments of thecommunication subsystem 434 could use an antenna for an RF link or anaudio transducer for an audio link.

Rounding out the subsystems in the control module 410 are a power supply436 and a clock supply 438. The power supply 436 supplies the voltagesand currents necessary for each of the other subsystems. The clocksupply 438 supplies substantially all of the other subsystems with anyclock and timing signals necessary for their operation.

It should be observed that while the memory subsystem 431 is illustratedin FIG. 4 as a separate functional subsystem, the other subsystems mayalso require various amounts of memory to perform the functionsdescribed above and others. Furthermore, while the control module 410 ispreferably a single physical unit contained within a single physicalenclosure, namely the housing 326 (FIG. 3), it may comprise a pluralityof spatially separate units each performing a subset of the capabilitiesdescribed above. Also, it should be noted that the various functions andcapabilities of the subsystems described above may be performed byelectronic hardware, computer software (or firmware), or a combinationthereof. The division of work between the CPU 432 and the otherfunctional subsystems may also vary—the functional distinctionsillustrated in FIG. 4 may not reflect the integration of functions in areal-world system or method according to the invention.

FIG. 5 illustrates the contents of the memory subsystem 431 and the datastructures it contains in a system according to the invention.

In particular, as described generally above and in detail below, theimplantable neurostimulator 110 is capable of detecting neurologicalevents and conditions characteristic of movement disorders, and iscapable of storing such information and communicating it to externalequipment such as the programmer 212.

A first storage facility 510 within the memory subsystem 431 is adaptedto store diagnostic records received from the implantableneurostimulator 110. In particular, the diagnostic records willgenerally include the time of and details regarding any neurologicalevents detected by the implantable neurostimulator 110 (such asinstances of detected tremor) or actions performed by the implantableneurostimulator 110. For tremor, the details stored among the diagnosticrecords 510 might include time of day, detected frequency (which, asdescribed above, generally does not vary much between instances in asingle patient), amplitude, and what therapeutic actions might have beentaken. Possible actions performed might include electrical stimulationapplied, mode changes, interrogation attempts, programming attempts, andother operations. For applied electrical stimulation, the specificdetails recorded among the diagnostic records might include time of day,stimulation waveform used, amplitude, and outcome (i.e., whether thetremor ceased).

A second storage facility 512 within the memory subsystem 431 is adaptedto store sensor data. The implantable neurostimulator 110 is capable ofrecording EEG data from the electrodes 412-418 and other sensor datafrom external sensors such as external sensor 421 and internal sensorssuch as internal sensor 422 when conditions dictate (e.g., immediatelybefore and after a detected event, on a scheduled basis, or uponcommand). For additional information on EEG recording in the context ofa neurostimulator used to treat epileptic seizures, see U.S. Pat. No.6,128,538 for “Means and Methods for the Treatment of NeurologicalDisorders,” filed on Nov. 29, 1999, and issued on Oct. 3, 2000. As wouldbe apparent to a practitioner of ordinary skill, similar considerationsapply to a system according to the present invention.

A third storage facility 514 within the memory subsystem 431 stores anyprogram code required for the CPU 432 and any other subsystems of theimplantable neurostimulator 110 to operate. In a preferred embodiment ofthe invention, the program code is updateable via data communicationsthrough the communication subsystem 434, thereby enabling theimplantable neurostimulator to be reprogrammed or modified as necessaryfor optimum patient treatment.

Finally, a fourth storage facility 516 within the memory subsystem 431includes any patient-specific and device-specific settings used in theoperation of the implantable neurostimulator 110. The programmer 212generates these settings based on patient-specific considerations,including the nature of the movement disorder being treated, thelocations of the electrodes and the types of sensors being used, and anyother relevant factors. Preferably, the programmer 212 is programmed togenerate these settings based on an analysis of the patient's EEG andother sensor data, which might have been acquired by and received fromthe implantable neurostimulator 110 or by other means. Examples ofpatient-specific parameters would include detection settings (e.g., theamplitude threshold used to identify tremor, as described below) andstimulation settings (e.g., the frequency of electrical stimulationapplied to terminate tremor). Many other parameters and settings are ofcourse possible and will not be described in detail here, as they wouldbe apparent to an individual of ordinary skill.

The memory subsystem 431 might also include various other types of data.It should be observed that the various data types described above areintended as illustrative and not comprehensive.

FIG. 6 depicts two waveforms. It will be observed that when tremor ispresent, an EEG signal waveform 610 representative of brain activityshares generally the same characteristics (frequency, generalmorphology) with an EMG signal waveform 612 representative ofneuromuscular activity. In particular, a first interval 614 representsthe interval between a first tremor burst 616 and a second tremor burst;that first interval 614 in general defines the wave duration (and hencefrequency) of the patient's tremor. This duration will vary from patientto patient, but is usually stereotypical of tremor experienced by asingle patient.

A second interval 620 represents the interval between a first landmark622 in the EEG signal 610 and a corresponding second landmark 624 in thesame patient's EMG signal 612. This second interval 620 defines thephase difference between the EEG signal 610 and the EMG signal 612. Aswith the duration and frequency, the phase difference is likely to varyfrom patient to patient but not within a single patient.

It will be recognized that the fixed frequency and phase differenceillustrated in FIG. 6 would tend to make tremor detection possible; amethod for accomplishing this is set forth in greater detail withreference to FIG. 9.

The waveforms 610 and 612 are intended for purposes of illustration offrequency and phase relationships only, and do not necessarily representany actual EEG or EMG signals likely to be found in an actual patient.In particular, the EMG signal waveform 612 is likely to have asubstantially different morphology with an increased signal-to-noiseratio in comparison to the EEG signal waveform 610. Other differencesmay also be present and will be understood by a practitioner of ordinaryskill.

In general, a process performed by the implantable neurostimulator 110for detecting a neurological event or characteristic such as tremor isset forth below, with reference to FIG. 7.

The process begins by receiving a signal (step 710) from one or morebrain or peripheral electrodes (such as the electrodes 412-418) or froman internal sensor 422 or an external sensor 421.

The signal is then processed as necessary (step 712) in the analogdomain to obtain a usable signal. For example, it may be necessary ordesirable to provide signal amplification or filtering to removeunwanted noise, extraneous information in frequency bands not beinganalyzed, stimulation and amplifier blanking artifacts, and the like.

The signal is digitized (step 714), i.e. the analog signal is convertedinto a digital data stream. The detection subsystem 423 operates andperforms the detection techniques described herein upon digital data,and other subsystems of the implantable neurostimulator 110 also operatein the digital domain. Preferably, digitization is performed at a rateof either 250 or 500 Hz and at a resolution of 8-10 bits.

The digital data is then processed (step 716) and transformed in thedigital domain as desired for detection and other purposes. At thisstage, after digitization of the signal, generally a digitalrepresentation of the analog signal has been obtained, but it may bedesirable to transform the data into the frequency domain or obtainother information about the signal through other transformations.

If desired, the digital data is stored (step 718) in the memorysubsystem 431, for later retrieval by external equipment. It will beappreciated (and has generally been set forth above) that it may bedesirable in some circumstances to store digital data representative ofepisodes of tremor or other symptoms for later diagnosis by a clinician;this capability may be invoked by programming the implantableneurostimulator 110 to record data at one or more specific times, byprogramming the neurostimulator 110 to store a specified quantity ofpre-trigger and post-trigger sensor data, or by any other desired andclinically advantageous means.

The data is then analyzed (step 720) by the detection subsystem 423 toidentify when tremor or other symptoms of the movement disorder areoccurring. The methods performed in identifying tremor, in particular,are described in greater detail below with reference to FIGS. 8, 9, 11,and 13.

The data analysis results are checked for the occurrence of an event(step 722), and if one has occurred, an action is performed by theimplantable neurostimulator 110. Such actions may include the deliveryof treatment (which will be discussed in greater detail below), thestorage of sensor data, the storage of a diagnostic record, or any otherclinically advantageous function.

The process illustrated by the flow chart of FIG. 7 is preferablyperformed in parallel for as many input channels as the implantableneurostimulator 110 has available. As described and illustrated above,one embodiment of the implantable neurostimulator includes eight inputchannels, any of which may be received from electrodes or other sensors.

As referenced above, one method for detecting tremor is illustrated inFIG. 8. The method begins by measuring the amplitude (step 810) of anelectrographic signal received from the electrodes 412-418 (or a signalreceived from some other kind of sensor, such as an accelerometer). Theamplitude is generally defined as the difference between the highestpositive-going peaks in the signal and the lowest negative-going peaks.

The average amplitude is then calculated over a period of time (step812). Preferably, the average amplitude is calculated over a period ofgreater than approximately one second, as this will allow anysignificant variations present within the 3-5 Hz tremor signals to beaveraged out, leaving only the average amplitude of the signalsrepresenting tremor.

A threshold is then calculated (step 814) or otherwise obtained. It isexpected that the amplitude of any observed electrographic tremor willvary depending on a number of factors, both from patient to patient andeven within a single patient. Accordingly, although a single programmedthreshold may function to detect tremor, it is believed advantageous tocalculate a dynamic threshold value. In an embodiment of the invention,the dynamic threshold is calculated to be a fixed offset or percentagegreater than a long-term moving average amplitude of the observed signalthat does not include tremor oscillations. This signal can be obtained,for example, from another portion of the patient's brain, or from atremor-free period (such as shortly after an episode of treatment). Ifinsufficient tremor-free signal data is available, the threshold can becalculated to be slightly lower than the average tremor oscillationamplitude experienced by the patient.

If the average amplitude of the signal exceeds the threshold (step 816),then a detection is triggered (step 818). Generally, as described ingreater detail below, the implantable neurostimulator 110 is programmedto perform an action when a detection is triggered—for example to applytherapeutic electrical stimulation or to deliver a dose of a medication.

Regardless of whether a detection has been triggered, an advantageousembodiment of the invention performs the method of FIG. 8 essentiallycontinuously (or when programmed to do so), thereby continuouslycalculating the average amplitude, updating the threshold, and checkingthe average amplitude of the signal against the threshold. It will berecognized that this procedure can be performed on multiple inputchannels, even more than one at the same time.

An alternative method for detecting tremor is illustrated in FIG. 9; itdetects tremor by relating the frequency and phase of a signal obtainedin the patient's brain to the frequency and phase of a signal obtainedin a limb that tends to experience tremor. As with the methodillustrated by FIG. 8, the method is operative on electrographic dataand other types of sensor data, including accelerometer measurements.However, for illustrative purposes, the method is described below withreference to EEG and EMG measurements.

The method begins by measuring a frequency of the patient's EEG (step910), at a location where tremor is generally observed (such as thethalamus). The frequency of the patient's EMG is also measured (step912). A signal's frequency can be calculated in several possible ways,including via Fourier (and more easily implemented FFT) transforms,measuring signal amplitude after band pass filtering, and via half waves(which will be illustrated and discussed in greater detail below). Thedifference between the EEG frequency and the EMG frequency is thencalculated (step 914).

The phase of the EEG signal is then observed and measured (step 916). Inan embodiment of the invention, phase is represented simply by the timeat which a measurable feature of a waveform occurs. For example, in FIG.6, the first landmark 622 of the patient's EEG signal occurs at ameasurable time identified with reference to the clock supply 438.Likewise, the phase of the corresponding EMG signal is observed andmeasured (step 918). In FIG. 6, the second landmark 624 of the patient'sEMG also occurs at a measurable time. The phase difference (in theexample of FIG. 6, namely the difference between the time of the firstlandmark and the time of the second landmark) is calculated (step 920).Preferably, phase measurements and calculations made according to theinvention are performed on heavily filtered or otherwise pre-processedsignals, so that the measured phase is that of any tremor, not someother feature of the signal (such as ordinary background EEG activity).

When tremor is occurring, it is expected that the patient's EEG and thepatient's EMG will both exhibit a measurable component at the samefrequency. Accordingly, when tremor is present, the frequency differencewill be near zero. Similarly, when tremor is present, the phase of thepatient's tremor oscillations in the EEG will bear a fixed relationshipto the phase of the patient's tremor oscillations in the EMG.Accordingly, the calculated phase difference will tend to remain near apatient-specific constant (which, in a preferred embodiment of theinvention, can be measured and programmed into the implantableneurostimulator 110). If both the frequency difference and the phasedifference are within range of their expected values (step 922), then adetection is triggered (step 924), and the device will generally performan action (such as apply a treatment, switch modes, or store one or moresignals for diagnostic purposes).

As with FIG. 8, the method illustrated in FIG. 9 can be performedcontinuously and on as many channels of data as desired or clinicallyrelevant.

Referring now to FIG. 10, one advantageous form of processing by thedetection subsystem 423, namely qualified half wave measurement, isdescribed in conjunction with a filtered and sampled waveform 1010. Thewaveform 1010 is considered herein to be generally representative of anEEG signal obtained and initially processed according to the invention.Initially, half waves in general will be described herein as backgroundinformation for the subsequent description of a detection methodemploying half waves.

In a first half wave 1012, which is partially illustrated in FIG. 10(the starting point occurs before the illustrated waveform segment 1010begins), the waveform segment 1010 is essentially monotonicallydecreasing, except for a small first perturbation 1014. Accordingly, thefirst half wave 1012 is represented by a vector from the starting point(not shown) to a first local extremum 1016, where the waveform starts tomove in the opposite direction. The first perturbation 1014 is ofinsufficient amplitude to be considered a local extremum, and isdisregarded by a hysteresis mechanism (discussed in further detailbelow). A second half wave 1018 extends between the first local extremum1016 and a second local extremum 1020. Again, a second perturbation 1022is of insufficient amplitude to be considered an extremum. Likewise, athird half wave 1024 extends between the second local extremum 1020 anda third local extremum 1026; this may appear to be a small perturbation,but is greater in amplitude than a selected hysteresis threshold. Theremaining half waves 1028, 1030, 1032, 1034, and 1036 are identifiedanalogously. As will be discussed in further detail below, each of theidentified half waves 1012, 1018, 1024, 1028, 1030, 1032, 1034, and 1036has a corresponding duration 1038, 1040, 1042, 1044, 1046, 1048, 1050,and 1052, respectively, and analogously, a corresponding amplitudedetermined from the relative positions of each half wave's startingpoint and ending point along the vertical axis, and a slope direction,increasing or decreasing. If a half wave's duration and amplitude bothexceed fixed or programmable thresholds, then the observed half wave islarge (and hence significant) enough to be considered a qualified halfwave.

In a method performed according to the invention, it is particularlyadvantageous to allow for a programmable hysteresis setting inidentifying the ends of half waves. In other words, as explained above,the end of an increasing or decreasing half wave might be prematurelyidentified as a result of quantization (and other) noise, low-amplitudesignal components, and other perturbing factors, unless a smallhysteresis allowance is made before a reversal of waveform direction(and a corresponding half wave end) is identified. Hysteresis allows forinsignificant variations in signal level inconsistent with the signal'soverall movement to be ignored without the need for extensive furthersignal processing such as filtering. Without hysteresis, such small andinsignificant variations might lead to substantial and gross changes inwhere half waves are identified, leading to unpredictable results.

As described above, measuring signal half waves is an advantageoustechnique in determining whether tremor is present in a measured signal,either EEG or from some other sensor. A method for using half waves toidentify tremor is illustrated in FIG. 11.

Initially, to isolate a signal suitable for half wave measurement, a lowpass filter is applied (step 1110) to a signal (such as an EEG signal)that tends to include information representative of tremor. As describedabove, an EEG signal (and to a lesser extent, an EMG signal) contains asignificant amount of information that is not related to tremor; much ofthis appears to be background activity; it generally appears infrequency bands outside of the 3-5 Hz band where tremor is usuallyfound. For half wave measurements to perform effectively in a systemaccording to the invention, as much of this noise as possible should beremoved. One way to accomplish this is through low-pass filtering. Othermethods are of course possible, one of which will be described belowwith reference to FIG. 13.

The parameters for qualified half wave detection are preferably set toidentify those half waves that are components of signals in the 3-5 Hzrange. Qualified half waves in the signal are then identified (step1112).

As described above, qualified half waves are generally counted within aspecified time window (which is preferably long enough to capture enoughhalf waves to reduce percentage errors caused by small perturbations inthe signal, for example five seconds).

A threshold is then calculated (step 1114) based on historical half wavemeasurements over a longer time period. Analogously to the amplitudethreshold-based tremor detection method illustrated in FIG. 8, thethreshold is preferably calculated as a fixed or percentage offset overa long-term trend of half wave measurements (e.g., over minutes) that donot represent tremor (or represent a clinically acceptable level oftremor), but if such a trend is not available, the threshold can becalculated to be slightly below typical observed tremor levels. Acombination of the approaches is also possible.

If the number of qualified half waves (that is, the number of half wavesof an amplitude and duration sufficient to be considered representativeof the signal) exceeds the threshold (step 1116), then a detection istriggered (step 1118) and the device generally is programmed to performan action.

As with FIGS. 8-9, the method illustrated in FIG. 11 can be performedcontinuously and on as many channels of data as desired or clinicallyrelevant.

As will be described in greater detail below, the area under the curveof a waveform is another useful calculation that can be employed in thedetection of tremor related to a movement disorder. The concept of areaunder a waveform's curve is described initially, and will providebackground information for the subsequent discussion of a detectionscheme that employs the calculation.

FIG. 12 illustrates the waveform of FIG. 10 with area under the curveidentified within an exemplary time window. Area under the curve, whichin some circumstances is somewhat representative of a signal's energy(though energy of a waveform is more accurately represented by the areaunder the square of a waveform), is another signal processing anddetection method used in accordance with the invention.

The total area under the curve represented by a waveform 1210 within thewindow 1212 is equal to the sum of the absolute values of the areas ofeach rectangular region of unit width vertically bounded by thehorizontal axis and the sample. For example, the first contribution tothe area under the curve within the window 1212 comes from a firstregion 1214 between a first sample 1216 and a baseline 1217. A secondcontribution to the area under the curve within the window 1212 comesfrom a second region 1218, including areas between a second sample 1220and the baseline 1217. There are similar regions and contributions for athird sample 1222 and the baseline 1217, a fourth sample 1224 and thebaseline 1217, and so on. It should be observed that the region widthsare not important—the area under each sample can be considered theproduct of the sample's amplitude and a unit width, which can bedisregarded. In a similar manner, each region is accumulated and addedto the total area under the curve within the window 1212. Although theconcept of separate rectangular regions is a useful construct forvisualizing the idea of area under a curve, it should be noted that aprocess for calculating area need not partition areas into regions asshown in FIG. 12—it is only necessary to accumulate the absolute valueof the waveform's amplitude at each sample, as the unit width of eachregion can be disregarded.

As described above, measuring signal half waves is an advantageoustechnique in determining whether tremor is present in a measured signal,either EEG or from some other sensor. An alternative method for usinghalf waves to identify tremor is illustrated in FIG. 13. It involvesusing an advantageous configuration for the detection of tremor, inwhich a signal area calculation is performed (as described above withreference to FIG. 12), and the resulting string of measurements is fedas a signal into a half wave calculation. This method is illustrated inFIG. 13.

Initially, to isolate a signal suitable for half wave measurement, thearea measurement scheme described above can be used to remove sensorsignal noise not relevant for tremor identification. Initially, an area(as described above) is calculated over a short time window, which inthe described embodiment is on the order of tens of milliseconds inlength (step 1310). As set forth above, an EEG signal (and to a lesserextent, an EMG signal) contains a significant amount of information thatis not related to tremor; much of this appears to be Gaussian noise; itgenerally appears in frequency bands outside of the 3-5 Hz band wheretremor is usually found. For half wave measurements to performeffectively in a system according to the invention, as much of thisnoise as possible should be removed, and the signal area calculated overa window tends to accomplish this. In addition to the low-pass filteringmethod described above and illustrated in FIG. 11, other methods arepossible and will be understood by a practitioner of ordinary skill inthe art. In particular, it will be recognized that it is also possibleto calculate the line length of the sensor signal (see U.S. Pat. No.8,810,285 to Pless et al. for “Seizure Sensing and Detection Using anImplantable Device,” filed on Jun. 28, 2001, issued Oct. 26, 2004, for adescription); this also tends to remove extraneous information from thesignal, but is believed to be more sensitive to transients and noisethan the area under the curve described above.

A sequence of area measurements for consecutive windows is therebygenerated, and that sequence of measurements is provided as an input toa half wave measurement function, using a time window substantiallylonger than that used for the area calculation.

The parameters for qualified half wave detection are preferably set toidentify those half waves that are components of signals in the 3-5 Hzrange. Qualified half waves in the signal are then identified (step1312).

As described above, qualified half waves are generally counted within aspecified time window (which is preferably long enough to capture enoughhalf waves to reduce percentage errors caused by small perturbations inthe signal, for example five seconds).

A threshold is then calculated (step 1314) based on historical half wavemeasurements over a longer time period. Analogously to the amplitudethreshold-based tremor detection method illustrated in FIG. 8, thethreshold is preferably calculated as a fixed or percentage offset overa long-term trend of half wave measurements (e.g., over minutes) that donot represent tremor (or represent a clinically acceptable level oftremor), but if such a trend is not available, the threshold can becalculated to be slightly below typical observed tremor levels. Acombination of the approaches is also possible.

If the number of qualified half waves (that is, the number of half wavesof an amplitude and duration sufficient to be considered representativeof the signal) exceeds the threshold (step 1316), then a detection istriggered (step 1318) and the device generally is programmed to performan action.

As with FIGS. 8, 9 and 11, the method illustrated in FIG. 13 can beperformed continuously and on as many channels of data as desired orclinically relevant.

FIG. 14 illustrates several possible waveform morphologies that might beadvantageously employed for the treatment of movement disorders with animplantable neurostimulator according to the invention.

A first waveform 1410 comprises a plurality of bursts of biphasicpulses. In an embodiment of the invention, it may be advantageous toapply several consecutive bursts of pulses, as illustrated, to disruptthe neurological activity that results in tremor. A limited number ofbursts may be applied at any given time. It should be recognized thatthe amplitude, duration, and inter-pulse interval for each pulse in aburst can preferably be varied by programming the implantableneurostimulator 110 accordingly. In an embodiment of the invention, eachpulse within a burst can be varied individually. Moreover, it ispreferably possible also to program different burst lengths andinter-burst intervals, as well as the number of bursts applied in anysingle treatment.

A second waveform 1412 comprises, as illustrated, a single burst ofbiphasic pulses. Unlike the bursts illustrated in the first waveform1410, however, the beginning of the burst “ramps” up to a maximumamplitude, and the end of the burst ramps back down to zero. Thismorphology is considered to provide some relief to patients whoexperience unpleasant sensory side effects when stimulation is abruptlybegun and ended.

In a manner similar to the first waveform 1410, the second waveform 1412can also be applied multiple times in succession if it is advantageousto do so. As with the first waveform 1410, numerous parameters can bevaried to different effect; durations for the beginning ramp-up and theending ramp-down are preferably also able to be specified and programmedin a system according to the invention according to a particularpatient's clinical needs.

A third waveform 1414 comprises a digitized approximation of asinusoidal morphology. This third waveform 1414 might be advantageouslyemployed to disrupt or otherwise terminate the symptoms of a movementdisorder in certain patients. In particular, the third substantiallysinusoidal waveform 1414 is particularly well suited to low frequencyuse.

A fourth waveform 1416 comprises a waveform similar to that of the thirdwaveform 1414, but with a direct current (DC) component added.Stimulation with small direct currents may be clinically advantageous incertain circumstances, but care must be taken to avoid charge densitiesthat might result in tissue damage.

It should be noted that the waveforms of FIG. 14 are not to scale, andin particular the relationship between pulse duration and inter-pulseinterval may be different in a functioning embodiment of the inventionfrom what is illustrated here. The waveforms illustrated in FIG. 14 arefor purposes of illustration only, and as would be recognized by apractitioner of ordinary skill in the art, would not necessarily beadvantageous in any particular clinical application.

Any of the waveforms of FIG. 14 are suitable for use in eitherresponsive stimulation or programmed stimulation according to theinvention, and will result in significant benefits in comparison tocontinuous stimulation when applied intermittently. One or more of thesewaveforms 1410-1416 can also be applied in conjunction with drug therapydelivered from the drug dispenser 430 (FIG. 4), either in the samelocation in the patient's body or in different locations.

FIG. 15 depicts a flow chart illustrating the method by which aneurostimulation system (such as the implantable neurostimulator device110, FIG. 1) provides adaptive and synchronized therapy according to anembodiment of the invention. Initially, as described above withreference to FIG. 7, the system receives EEG data or otherelectrographic or sensor signals—this is generally performed on acontinuous basis, alongside and in parallel with any other detection andother operations performed by the neurostimulator device 110. Alsopreferably concurrently, the EEG data is processed, analyzed, andstored.

A neurological event is then detected (step 1510), or some othertime-related event occurs (such as receipt of a time schedulinginterrupt from the CPU 432). Following the event, a treatment waveform,including stimulation time and signal details, is generated (step 1512).The treatment waveform generation process for synchronized stimulationis illustrated in FIG. 17 and described below, and generally involvesextracting information from a measured electrographic signal via thedetection subsystem 423 and generating a waveform representative of anadaptive stimulation signal based on the extracted information.Otherwise, any desired waveform (such as those illustrated in FIG. 14)can be employed, and need not be created in real time.

Application of the generated stimulation therapy is then initiated (step1514) at the appropriate time. The process used to initiate therapy isdescribed below. Preferably, stimulation is applied in parallel withother operations performed by the implantable neurostimulator device110, so even while stimulation is ongoing, if the neurostimulator device110 is not finished applying adaptive stimulation therapy (step 1516),the process of FIG. 15 can repeat as necessary.

Therapy is initiated and applied at a clinically appropriate timeaccording to the methods described below. Delivery of stimulation isscheduled by the CPU 432 (FIG. 4) and tied to a timer interrupt. Whenthe timer interrupt is received, synchronization to the therapy schedulehas been accomplished, and the CPU 432 commands the therapy subsystem424 (and in particular the appropriate responsive stimulation 428 ordrug therapy 429) to deliver the appropriate therapy, thereby applyingstimulation therapy to the patient. The nature of the desiredstimulation waveform, if it is simple, can be expressed in the commandfrom the CPU 432, or alternatively, a representation of the desiredstimulation waveform, if stored in the memory subsystem 431, can becaused by the CPU 432 to be streamed to the stimulation subsystem 424.If there are additional scheduled pulses or waveforms to be applied, thetherapy plan is optionally revised, and the synchronization andapplication steps are repeated as necessary.

As generally described above and as considered in greater detail below,it may be clinically advantageous and particularly effective tosynchronize bursts of electrical stimulation treatment with theoscillations of tremor. This can be accomplished with either responsiveelectrical stimulation or programmed electrical stimulation. Thissynchronization is illustrated in FIG. 16.

As illustrated, the beginning of a first stimulation burst 1610 issynchronized with a first early identifiable feature 1612 of a firsttremor burst 1614. At this time, the abnormal neurological activitycharacterizing tremor is at its peak. Similarly, the beginning of asecond stimulation burst 1616 (immediately following the firststimulation burst 1610) is synchronized with a second early identifiablefeature 1618 of a second tremor burst 1620. The first early identifiablefeature 1612 and the second early identifiable feature 1618 areadvantageously identified in a neurostimulator 110 according to theinvention by the detection methods described in detail herein. Inparticular, the threshold method (FIG. 8) and the frequency/phase method(FIG. 9) can be used to quickly identify activity of high magnitude in aparticular frequency band. Alternatively, half wave detection (FIG. 11)can be calibrated to identify particularly large qualified half waves,which would tend to indicate a maximum in the relevant tremor burst,rather than the beginning,

The process advantageously used in generating such synchronizedtreatment bursts is set forth below.

One process for generating a synchronized treatment waveform isillustrated in detail in FIG. 17. Initially, a time synchronizationpoint is identified (step 1710). As described above, this is generallyaccomplished by identifying a specific half wave of interest andestablishing the end point of that half wave as a reference point forthe synchronization point (though other reference points are alsopossible, based on processing windows, real time, and other timersaccessible by a neurostimulator according to the invention). The processof identifying a time synchronization point is illustrated in detail inFIG. 18 and will be described below. The synchronization point is usedby the CPU 432 to schedule therapy application (step 1712) by setting upa specific timer interrupt according to the clock supply 438 (FIG. 4). Atherapy pattern template (for example, a single pulse, a burst ofpulses, or some other waveform) is then selected and associated with theschedule (step 1714). In the disclosed embodiment of the invention, oneor more possible therapy templates are stored in the memory subsystem431 and are made accessible to the CPU 432 and the stimulation subsystem424. These templates, in an embodiment of the invention, represent oneor more of the available stimulation waveforms, such as the onesillustrated in FIG. 14. It should be noted, however, that if selectionof a desired template from a plurality of templates is not an aspect ofthe particular adaptive stimulation employed in an embodiment of theinvention, then selection of a template (step 1714) can be performedbefore the synchronization point is identified (step 1710) or thetherapy application is scheduled (step 1712); template selection in sucha circumstance does not need to be in a time-critical processing path.

It should be noted that the synchronization point may be obtained fromsubstantially any input channel of a neurostimulator according to theinvention. To synchronize stimulation to a neurologically significantinput signal, it is generally most effective to use the same inputchannel for event detection, synchronization, and stimulation. However,to achieve intentional desynchronization or other alteration accordingto the invention, it may be preferable to derive the synchronizationinformation from a separate channel, which is more likely to havecharacteristics that are substantially independent from and unaffectedby a channel used for detection, stimulation, or transformation of atherapy template. The synchronization point may further be obtained orderived from some other source of information less directly associatedwith or even unrelated to input channels, such as the clock supply 438(FIG. 4); this would also tend to achieve variability with respect toneurological activity.

In an alternative embodiment of the invention, three separate channelsmay be used for event detection, synchronization and extraction ofparameters for therapy template transformation, and stimulation. And ina further embodiment, four separate channels may be used for eventdetection, synchronization, extraction of parameters for therapytemplate transformation, and stimulation. It is particularlyadvantageous to be able to provide as much configuration flexibility aspossible for varying patient clinical needs.

Although it is generally considered advantageous to be able to modify asingle therapy pattern template via characteristics of a measuredelectrographic signal, it should be observed that in an embodiment ofthe invention, one aspect of the waveform generation process might be toselect a desired template from a collection of multiple templates basedon signal characteristic.

A stimulation waveform is then generated (step 1716) according to theselected therapy template and any desired parameters identified in thesynchronization point. Data representative of the actual stimulationwaveform, as generated and based upon the therapy template and theparameters of the synchronization point, are stored in the memorysubsystem 431 for access by the stimulation subsystem 424.

To generate the stimulation waveform according to the selected therapytemplate and any desirable characteristics extracted from thesynchronization point, as indicated in step 1716, a system or methodaccording to the invention is capable of transforming the therapytemplate in various ways. For example, as described above, the time ofthe synchronization point is generally used to schedule the delivery ofthe stimulation waveform. In an alternative embodiment of the invention,the waveform is generated according to not only time synchronizationinformation, but also according to other aspects of the synchronizationpoint.

For example, if the synchronization point represents a qualified halfwave, the time, amplitude, and duration of the qualified half wave andthe interval between qualified half waves can be used to select or alterthe polarity or amplitude of one or more pulses in the stimulationwaveform or the therapy template as a whole; to govern the frequency,inter-pulse interval, or pulse width of the stimulation waveform if thedesired therapy template is a burst of pulses or some other repeatingpattern; or to choose one of a set of possible therapy templates bymapping the desired characteristic of the synchronization point onto alook-up table of therapy templates.

It should be noted that for purposes of increased variation according tothe invention, it is not necessary to map electrographic signalcharacteristics to their analogous counterparts in the stimulationwaveform. For example, it may be appropriate in certain circumstances tocause the amplitude of a qualified half wave to modify the duration of astimulation waveform, or for a qualified half wave duration to specifythe maximum amplitude in a burst of pulses. Preferably, aneurostimulator according to the invention is programmable to accomplishwhatever form or combination of adaptive stimulation characteristics isfound to be advantageous in a particular clinical setting.

In a maximally flexible embodiment of the invention, after each pulse orwaveform segment is delivered, the remaining portion of a therapy plancan be revised, resynchronized, retransformed, or otherwise altered in amanner similar to that set forth in FIG. 17 and described below. Inparticular, it would be advantageous, if desired, to be able to identifya new synchronization point (step 1710) and reschedule therapy (step1712), thereby allowing each pulse or segment of a stimulation waveformto be individually synchronized, correlated, or otherwise altered withrespect to a sensed signal. It may also be advantageous in somecircumstances to be able to select a new therapy pattern template (step1714) or regenerate the therapy waveform (step 1716), or both, accordingto newly measured characteristics of an input electrographic waveform onany desired channel of the neurostimulator device 110.

In an embodiment of the invention, to achieve variation in stimulationtiming, it may be possible to synchronize the delivery of stimulation toevents other than a synchronization point (step 1710) that correspondsto some characteristic or feature of an electrographic signal. Forexample, it may be desirable to synchronize to timer interruptsgenerated by the clock supply 438 of the neurostimulator device 110, orto any other event or time ascertainable by a subsystem of theneurostimulator device 110.

As described above, the therapy application process of the inventionpreferably is able to operate in parallel with other operationsperformed by the implantable neurostimulator device 110 (FIG. 1).

As generally described above, the method used to identify asynchronization point in an embodiment of the invention is shown indetail in FIG. 18. When a neurological event is detected or theapplication of adaptive or synchronized stimulation is deemed desirable,the most recent measurement of a physiological condition (e.g., a halfwave extracted from an EEG signal, an EMG area measurement, etc.) isidentified (step 1810), and a desired parameter (namely one or more ofthe time stamp, duration, amplitude, or possibly other parametersrelated to the measurement) is extracted (step 1812). The extractedparameter is then transformed as desired (step 1814), either linearly ornonlinearly. For example, the extracted parameter can be transformedlinearly in one advantageous embodiment by multiplying it by a fixed orvariable scale factor and adding a fixed or variable offset. In anembodiment of the invention, stimulation can be approximatelysynchronized to the analyzed EEG waveform by scheduling a stimulationpulse to occur after the end of the most recent qualified half wave (ofsufficient amplitude and duration to suggest tremor) by a fixed delaybetween approximately 0 and 1000 milliseconds, a percentage of the delaybetween 0 and 100% of the measured interval between the 3-5 Hz tremoroscillations, or a combination of fixed and interval-dependent delays.In the disclosed embodiment of the invention, the measured intervalbetween waves is preferably calculated as the time delay betweensuccessive qualified half waves, as stored in a FIFO queue.

If desired, the parameters extracted from recent qualified half waves,as transformed, are constrained by minimum and maximum values (step1816). Preferably, the adaptive interval-based delay described above isconstrained by programmable minimum and maximum values between about 0and 1000 milliseconds.

For a burst of pulses, not only can the timing of the first pulse begoverned by a fixed or interval-dependent delay, but the inter-pulseinterval can also be controlled in a similar manner. For example, eitherthe duration or the interval of qualified half waves in the FIFO queuecan be used to control the inter-pulse interval, and qualified half waveamplitudes can be used to modify the amplitudes of subsequent pulses, orof the burst as a whole. Generally, controlling the parameters of eachpulse of a burst separately would be advantageously accomplished byscheduling each pulse in the burst as a separate stimulation event, andcausing the methods of the invention to extract information from theelectrographic signal and generate an adaptive pulse for each separatelyscheduled stimulation event.

Many possible uses of the parameters described above are possible. Toprovide decorrelation, rather than synchronization, as discussed above,it is possible to map qualified half wave duration or interval tostimulation amplitude, or qualified half wave amplitude to stimulationtiming or frequency, for example. In other detection schemes, such asthose reliant on waveform line length or area, as described above,parameters related to those measurements can also be used to provide ameasure of variability to a stimulation signal.

Similar waveform shaping and timing considerations can be applied toother stimulation waveforms, as well. To provide but one example, thefrequency of sinusoidal stimulation may be derived from the half waveinterval. Other possibilities consistent with the invention should beapparent.

It should be observed that while the foregoing detailed description ofvarious embodiments of the present invention is set forth in somedetail, the invention is not limited to those details and an implantableneurostimulator or other device made according to the invention candiffer from the disclosed embodiments in numerous ways. In particular,it will be appreciated that embodiments of the present invention may beemployed in many different applications to detect and treat movementdisorders and other conditions via responsive electrical stimulation ina patient's brain. It will be appreciated that the functions disclosedherein as being performed by hardware and software, respectively, may beperformed differently in an alternative embodiment. It should be furthernoted that functional distinctions are made above for purposes ofexplanation and clarity; structural distinctions in a system or methodaccording to the invention may not be drawn along the same boundaries.Hence, the appropriate scope hereof is deemed to be in accordance withthe claims as set forth below.

What is claimed is:
 1. An implantable neurostimulator for treating apatient experiencing a movement disorder comprising: a sensor interfacefor receiving a first signal from a first sensor configured to senseelectrical activity of the brain and a second signal from a secondsensor configured to sense motion of the patient; a detection subsystemfor analyzing the first signal and the second signal, the detectionsubsystem configured to: measure a frequency of the first signal and afrequency of the second signal, calculate a frequency offsetcorresponding to the difference between the frequency of the firstsignal and the frequency of the second signal, compare the frequencyoffset to a frequency criterion, measure a phase of the first signal anda phase of the second signal; calculate a phase offset corresponding tothe difference between the phase of the first signal and the phase ofthe second signal, compare the phase offset to a phase criterion, anddetect a tremor event when both the frequency criterion and thethreshold criterion are satisfied; and a stimulation subsystemconfigured to deliver a treatment to the patient from theneurostimulator.
 2. The implantable neurostimulator of claim 1, whereinthe frequency criterion is an offset value and the frequency criterionis satisfied when the frequency offset is within a specified range ofthe value.
 3. The implantable neurostimulator of claim 2, wherein theoffset value is near zero.
 4. The implantable neurostimulator of claim1, wherein the phase criterion is an offset constant and the phasecriterion is satisfied when the phase offset is within a specified rangeof the offset constant.
 5. The implantable neurostimulator of claim 4,wherein the offset constant is a patient-specific constant.
 6. Theimplantable neurostimulator of claim 1, wherein in order to measure aphase of the first signal and a phase of the second signal, thedetection subsystem is further configured to: determine a first time atwhich a first landmark of a waveform representative of the first signaloccurs; and determine a second time at which a second landmark of awaveform representative of the second signal occurs, the second landmarkbeing the same type of landmark as the first landmark.
 7. Theimplantable neurostimulator of claim 6, wherein the waveformrepresentative of the first signal comprises a plurality of peaks andthe first landmark corresponds to the largest peak of the plurality ofpeaks, and the waveform representative of the second signal comprises aplurality of peaks and the second landmark correspond to the largestpeak of the plurality of peaks.
 8. The implantable neurostimulator ofclaim 1, wherein the first and second signal are continuously receivedby the sensor interface and continuously analyzed by the detectionsubsystem.
 9. The implantable neurostimulator of claim 8, wherein thestimulation subsystem is configured to: deliver treatment for so long asthe tremor event is detected; and cease delivery of the treatment whenthe tremor event is no longer detected.
 10. A method for treating amovement disorder in a human patient with an implantable neurostimulatorcomprising: receiving a first signal from a first sensor configured tosense electrical activity of the brain; receiving a second signal from asecond sensor configured to sense motion of the patient; analyzing thefirst signal and the second signal to determine whether a tremorcharacteristic of an episode of the movement disorder is occurring,wherein analyzing the first and second signals comprises: measuring afrequency of the first signal and a frequency of the second signal,calculating a frequency offset corresponding to the difference betweenthe frequency of the first signal and the frequency of the secondsignal, comparing the frequency offset to a frequency criterion,measuring a phase of the first signal and a phase of the second signal;calculating a phase offset corresponding to the difference between thephase of the first signal and the phase of the second signal, comparingthe phase offset to a phase criterion, and detecting a tremor event whenboth the frequency criterion and the threshold criterion are satisfied;and delivering a treatment to the patient from the neurostimulator. 11.The method of claim 10, wherein the frequency criterion is an offsetvalue and the frequency criterion is satisfied when the frequency offsetis within a specified range of the offset value.
 12. The method of claim11, wherein the offset value is near zero.
 13. The method of claim 10,wherein the phase criterion is an offset constant and the phasecriterion is satisfied when the phase offset is within a specified rangeof the offset constant.
 14. The method of claim 13, wherein the offsetconstant is a patient-specific constant.
 15. The method of claim 10,wherein measuring a phase of the first signal and a phase of the secondsignal comprises: determining a first time at which a first landmark ofa waveform representative of the first signal occurs; and determining asecond time at which a second landmark of a waveform representative ofthe second signal occurs, the second landmark being the same type oflandmark as the first landmark.
 16. The method of claim 10, wherein thewaveform representative of the first signal comprises a plurality ofpeaks and the first landmark corresponds to the largest peak of theplurality of peaks, and the waveform representative of the second signalcomprises a plurality of peaks and the second landmark correspond to thelargest peak of the plurality of peaks.
 17. The method of claim 10,wherein the first and second signal are continuously received andanalyzed.
 18. The method of claim 17, wherein the treatment is deliveredfor so long as the tremor event is detected, the method furthercomprising ceasing delivery of the treatment when the tremor event is nolonger detected.